TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15053	45382;45383;45384	chr2:178621667;178621666;178621665	chr2:179486394;179486393;179486392
N2AB	13412	40459;40460;40461	chr2:178621667;178621666;178621665	chr2:179486394;179486393;179486392
N2A	12485	37678;37679;37680	chr2:178621667;178621666;178621665	chr2:179486394;179486393;179486392
N2B	5988	18187;18188;18189	chr2:178621667;178621666;178621665	chr2:179486394;179486393;179486392
Novex-1	6113	18562;18563;18564	chr2:178621667;178621666;178621665	chr2:179486394;179486393;179486392
Novex-2	6180	18763;18764;18765	chr2:178621667;178621666;178621665	chr2:179486394;179486393;179486392
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-102
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.1977
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
E/Q	None	None	1.0	N	0.576	0.405	0.37097340754	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
E/A	0.43	ambiguous	0.4682	ambiguous	-0.886	Destabilizing	0.999	D	0.619	neutral	D	0.607372493	None	None	N
E/C	0.9773	likely_pathogenic	0.9835	pathogenic	-0.551	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/D	0.3828	ambiguous	0.463	ambiguous	-1.33	Destabilizing	0.999	D	0.441	neutral	D	0.598707935	None	None	N
E/F	0.9521	likely_pathogenic	0.958	pathogenic	-0.564	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/G	0.6066	likely_pathogenic	0.635	pathogenic	-1.254	Destabilizing	1.0	D	0.731	prob.delet.	D	0.635599046	None	None	N
E/H	0.838	likely_pathogenic	0.8726	pathogenic	-0.96	Destabilizing	1.0	D	0.656	neutral	None	None	None	None	N
E/I	0.7158	likely_pathogenic	0.751	pathogenic	0.119	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/K	0.4919	ambiguous	0.5527	ambiguous	-0.918	Destabilizing	0.999	D	0.482	neutral	D	0.537775796	None	None	N
E/L	0.8198	likely_pathogenic	0.854	pathogenic	0.119	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/M	0.7923	likely_pathogenic	0.8131	pathogenic	0.654	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/N	0.6753	likely_pathogenic	0.7375	pathogenic	-1.283	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/P	0.9888	likely_pathogenic	0.9898	pathogenic	-0.194	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/Q	0.3552	ambiguous	0.3817	ambiguous	-1.14	Destabilizing	1.0	D	0.576	neutral	N	0.506932694	None	None	N
E/R	0.6868	likely_pathogenic	0.731	pathogenic	-0.728	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/S	0.5258	ambiguous	0.5667	pathogenic	-1.64	Destabilizing	0.999	D	0.541	neutral	None	None	None	None	N
E/T	0.52	ambiguous	0.5782	pathogenic	-1.337	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/V	0.5064	ambiguous	0.5431	ambiguous	-0.194	Destabilizing	1.0	D	0.77	deleterious	D	0.549617585	None	None	N
E/W	0.9871	likely_pathogenic	0.9894	pathogenic	-0.445	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/Y	0.9245	likely_pathogenic	0.937	pathogenic	-0.356	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.